1. Rectal drug administration
Dr Mohammad Issa

2. Rectal drug administration advantages
a relatively large dosage form can be accommodated in the rectum
the rectal route is safe and convenient for elderly and young patients
drug dilution is minimized as the residual fluid volume is low
the rectum is generally empty
absorption adjuvants have a more pronounced effect than in the upper gastrointestinal tract
degradative enzymes in the rectal lumen are at relatively low concentrations
therapy can easily be discontinued
first-pass elimination of drug by the liver is partly avoided

3. Barriers for drug absorption following rectal administration
If the drug is administered as a suppository, melting or liquefaction of the base has to occur and the degree of this will partly determine the spreading of the dose through the rectum. The drug must then dissolve in the limited rectal fluid available, which has been estimated to be between 1 and 3 ml
The amount of drug available for absorption can be further reduced by degradation by luminal contents, adsorption to luminal contents and defaecation. The drug must then diffuse across the unstirred water and mucous layers adjacent to the epithelium

4. Drug absorption and avoidance of first-pass metabolism
Drugs may be absorbed across the epithelial cell or via tight junctions, and it is believed that only passive transport occurs
Venous return from the colon and upper rectum is via the portal vein to the liver. If a drug is delivered to the upper part of the rectum, it is transported into the portal system, and is therefore subject to first pass metabolism in the liver.
The only way of avoiding first-pass metabolism is to deliver the drug to the lower part of the rectum
A 100% increase in the availability of lignocaine was demonstrated when administered rectally rather than orally, and it was calculated that the mean fraction of the rectally administered dose escaping first-pass metabolism was 57%

6. Dosage forms for rectal delivery
Suppositories: are normally either solid suspensions or solid emulsions
Rectally administered gelatin capsules: can contain liquid formulations
Enema: Micro-enemas have a volume of between 1 and 20 ml and macro enemas 50 ml or more, both of which may be administered as either solutions or suspensions

7. Adjuvants and enhancers
Transport from the rectal epithelium primarily involves two transport processes: paracellular and transcellular routes.
As in other parts of the gut, the opening of tight junctions by absorption enhancers has been extensively investigated
Putative enhancers include enamine derivatives, salicylates, calmodulin inhibitors, surfactants, chelating agents, fatty acids and lectins

8. Adjuvants and enhancers
Bioavailability of a small peptide such as vasopressin is increased to nearly 30% in the presence of sodium taurodihydrofusidate
It should always be borne in mind that the enhancement via the paracellular route is non-selective, with the risk of absorption of bacterial endotoxins caused by lysis of bacterial cell walls

9. Therapeutic agents administered rectally
Anticonvulsants
Preoperative medication and induction of anaesthesia
Analgesics and antiarthritics
Antiemetics
Antibacterial agents
Xanthines
Drugs in inflammatory bowel disease
Cardiovascular active drugs